In cancer patients, determination of whether a malignancy has spread is the single most important factor used to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is of paramount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliably detect and diagnose micrometastases in lymph nodes. Thus, there is an urgent clinical need for an imaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliably detect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in vivo, noninvasive, molecular specific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targeted plasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph node micrometastases in real time. The first aim of the project is to develop a combined photoacoustic and ultrasound imaging system and protocol. The system will consist of a high frequency ultrasound machine coupled with a pulsed nanosecond tunable laser. The second aim is to develop spectroscopic image processing algorithms to detect sentinel lymph node metastasis after the injection of plasmonic nanosensors. The imaging system and algorithms will be tested on in vitro cell samples of nanosensors incubated with normal and cancerous cells. The final aim is to use the imaging system and spectroscopic algorithms to detect lymph node micrometastases in a murine cancer model in vivo. The imaging results will be correlated with histology of the resected lymph nodes. The training plan proposed to accomplish these goals has been designed to establish trainee mentors with specific technical expertise. The selected mentors are experts in ultrasound and photoacoustic imaging and image processing. The PI will enroll in formal training in the ethical conduct of research and in training specific to his research field, to prepare him for independent research.